PROJECT SUMMARY The present application builds on recent research in our laboratory showing that social visual engagement?the way in which infants visually explore, engage, and ultimately learn from and adapt to their surrounding world? is (1) tightly coupled to genetic variation, with concordance in identical toddler twins equal to 0.91; (2) highly phylogenetically conserved, with infant rhesus monkeys exhibiting patterns of early eye-looking that are strikingly homologous to human infants; and (3) pathognomonically impaired in infants later diagnosed with ASD, with differences observed from at least month 2 onwards in initial and replication cohorts. The present application will build on these findings to study pivotal transitions in early infancy that set the stage for future attainment of social- communicative milestones. We will investigate early infant transitions from reflex-like to volitional social adaptive action in the first 2 months post-partum (Aim 1); the emergence of reciprocal and contingent infant social interaction (Aim 2); and the cascading consequences of very early infant social engagement?or the disruption thereof in ASD?on later, long-term social-communicative outcomes (Aim 3). Finally, we will connect these measures to concomitant changes in developing structural and functional brain networks (in Projects III and V), to the emergence of spoken communication (in Project II), and to response to early social interaction therapy (in Project IV). A cohort of 250 infants will be enrolled, consisting of infant siblings of children with autism who are at High Risk for developing ASD (HR-ASD, N=150) as well as infant siblings at Low Risk of developmental delays, with Typical Development expected by virtue of having no familial history of ASD (LR-TDx, N=100). Data will be collected longitudinally and prospectively, beginning in the first week after birth. This project directly addresses several of the aspirational goals for autism set forth by the NIH Interagency Autism Coordinating Committee, with emphasis on understanding the unfolding developmental trajectories, underlying mechanisms, and biological signatures of ASD.